T cell antigen Recognition. Role of MHC Flashcards
what is a major difference between BCR and TCR?
TCR cannot recognize free antigen (unprocessed). It can only recognize processed
antigen epitope in the form of a small linear peptide presented to it by antigen presenting cells (APCs, macrophages and dendritic cells) via MHC
what are the two major classes of TCR?
α, β TCR and the γ, δ TCR
what are very efficient as APCs due to their large surface areas and multiple appendages?
dendrites
what is the CD8+ T cell MHC class I restricted relationship?
MHC class I molecule on a macrophage is expressing a linear peptide to a TCR on a T cell that co-expresses a CD8 molecule that is associated with the MHC
what is the result of activation of aïve CD8+ T cell?
memory CD8+ T cells and effector CD8+ T cells, the cell killers
true or false: CD8+ T cells are labeled as intracellular killer cells
false: extracellular
what is the function of CD8+ T cells?
target abnormal cells and kill them
all nucleated cells express MHC class 1 molecules, why is this important?
This allows the CD8+ T cells to scan any nucleated cell looking for abnormal cells.
These “abnormal cells” are typically viral or bacterial infected cells or cancer cells
how do viral-infected cells and cancer cells try to hide from the CD8+ T cells?
by downregulating or altering the expression of the MHC class I molecule preventing foreign antigen peptide presentation
what does the innate extracellular killer, NK, do to combat viral or cancer cells hiding?
screens for the presence and structure of the MHC class I molecule on the surface of nucleated cells. If it is absent or defective, the NK cells also destroy the abnormal cell by apoptosis
what is the difference between CD4+ T cell MHC Class II restricted and CD8+ T cell
MHC Class I restricted?
naïve CD4+ T cells when activated yield memory CD4+ T cell and effector CD4+ T cells that either interact with B cells to guide isotype-switching or produce a number of different cytokines that help regulate an immune response
what expresses MHC class II molecules?
APC (macrophages, dendritic and select B cells)
true or false: the APCs express both MHC class I and MHC class II molecules on their surfaces.
true
why is tissue typing of the HLA critical for organ transplants?
each individual’s MHC class I and class II molecules can differ from another individual.
where can differences in MHC between different individuals in the same species can arise from?
multiple genes (polygenicity) or the genes can exist as multiple stable forms (polymorphisms)
what are the molecules that are independent genes found on chromosome 6 that code for the MHC class I?
HLA-A, HLA-B, HLA-C
Unique to the MHC class I molecule is a bound molecule called ________________ that is coded for independent of the HLA complex on chromosome 15
β2-microglobulin
what are MHC class II molecules are coded for by?
HLA-DP, HLA-DQ and HLA-DR.
Variation within a gene can translate to a _________________ different protein coded by that gene, which is the definition of polymorphism
phenotypically
why is it that the more ethnically and racially different two individuals are the greater the difference in their HLA proteins and the poorer they are a match for a tissue transplant?
Of all the gene complexes in the body that code for proteins, the MHC complex has most highly polymorphic genes and thus the greatest variation in the HLA proteins that are produced
true or false: Since the writing of this book, HLA-DM and HLA-DO have been also described on MHC class II molecules in increasing the number from 6 to 10 possible combinations accounting for variation from both parental chromosomes.
true
when does MHC class I molecule present foreign antigen?
when the host ‘s immune system deems detrimental to the cell.
why are the α1 and α2 regions classified as the variable region and the remaining region is classified as the invariant region?
the highly variable α1 and α2 regions of the α heavy chain forms the peptide-binding groove unique to each MHC class I molecule.
regarding MHC class I, is what determines the structural conformation of the peptide-binding groove and how are the peptides to be presented and selected?
Most of the variation in the amino acid sequences are localized to the α1 and α2
regions, which impact the conformation of the walls and floor of the binding groove. In
addition, the variable amino acid sequences create gaps or pockets in the floor that impact the selection of the linear peptide as well as its alignment in the binding groove to facilitate
presentation to the T cell
what does the peptide contain that align with allelic-specific gaps or pockets of each α1 and α2 region?
anchor residues
what is the significance of the presence or absence of anchor residues?
determine whether a linear peptide will or will not be selected for presentation to the T cell
(also that the seating of the anchor residues in the pockets ensures a stable presentation of the linear peptide to the T cell)
what is the primary function of MHC class II molecule?
present processed antigen in the form of a linear peptide to CD4+ helper T cells to increase in immune response
what are the α1and β1 regions of the MHC class II molecule classified as?
variable regions
what are α2 and β2
invariant regions
Upon binding of the TCR to linear peptide
presented by MHC class II, the CD4 cell surface protein on the T cell binds to the invariant __ region
β2
Given MHC class II molecule’s larger size based on molecular weight, it presents with a larger binding groove and thus, can accommodate linear peptides consisting of ______ amino acids in length
12-17
the linear peptides associated with the MHC class I molecule range between ______ amino
acids in length.
8-10
how does MHC class II molecule select for linear peptides to present to TCR?
- the linear peptides need to contain anchor residues (3-4) that can structurally bind to the
allelic-specific pockets located within the peptide-binding groove. This allows for greater
variability of the remaining amino acids not functioning as anchor residues yield a much larger and diverse pool of linear epitopes for recognition by the TCR. - the anchoring of the peptide to the binding groove provides structural stability of the linear peptide.
what is MHC restriction?
TCR recognizing the structural confirmation
of the linear peptide that is presented via the MHC on the APC.
